New book, 'Untangling the Double Helix,' explores enzymes responsible for maintaining genome...( COLD SPRING HARBOR N.Y. If it were ...)

COLD SPRING HARBOR, N.Y. If it were not for a group of enzymes called topoisomerases, DNA would become a knotted, coiled, dysfunctional mess inside of a cell as it gets twisted, rolled, unzipped, and pulled by the cellular machinery that reads and copies its sequence. Topoisomerases, which are responsible for relieving this tension and maintaining the integrity of the genome, were first discovered in the 1970s by Harvard's Professor of Biochemistry and Molecular Biology James C. Wang. Wang has written a book that discusses the history of topoisomerases, their mechanisms of action, and their use and potential as therapeutic targets. The book, entitled Untangling the Double Helix, has just been released by Cold Spring Harbor Laboratory Press.

"The primary motivation for [writing this book] is that, despite the gradual recognition of the significance of the DNA entanglement problem in nearly all cellular transactions of DNA, and the finding that many antimicrobial and anticancer therapeutics target the DNA topoisomerases, few articles have been written for the general readership," wrote Wang. The book will appeal to those with a general interest in molecular biology, the biological and clinical aspects of topoisomerase function, or in the mathematics and physics of topology.

Wang starts with the history of the "insuperable" DNA entanglement problem and describes research that led to the discovery of the DNA topoisomerases. He details the mechanistic features of the different subfamilies of DNA topoisomerases, and explains how cutting-edge laboratory techniques are used to visualize individual enzymes in real time as they break and rejoin DNA molecules in a controlled manner.

Wang describes how topoisomerases perform their magic in DNA replication, transcription, genetic recombination, and chromosome condensation, and ends with a discussion of topoisomerases as targets of therapeutic agents, including antibiotics (such as Ci
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